Effects of neostigmine on bronchoconstriction with continuous electrical stimulation in ratsEffects of neostigmine on bronchoconstriction with continuous electrical stimulation in rats持続的電気刺激によるラット気管収縮に対するネオスチグミンの効果

PURPOSE: When neostigmine is used to reverse muscle relaxants in patients with asthma without signs of airway inflammation, asthma attack is occasionally encountered. It is likely that abnormally increased electrical impulses traveling from the brain through cholinergic nerves to airway smooth muscles may be one of the pathogeneses of asthma attack. We applied continuous electrical field stimulation (c-EFS) or continuous electrical stimulation (c-ES) of low frequency to the vagal nerve of the rat in vitro and in vivo to determine the role of cholinergic nerve activation in inducing airway constriction. METHODS: Fifty-seven male Wistar rats were used. In an in vitro study we examined whether tetrodotoxin (TTX), an Na(+)-channel blocker, 4-DAMP, a muscarinic M(3) receptor antagonist, or neostigmine could affect c-EFS-induced contraction of the tracheal ring. In an in vivo study, we examined whether c-ES of the vagal nerve could increase maximum airway pressure (P (max)) and whether neostigmine could potentiate c-ES-induced P (max). RESULTS: TTX and 4-DAMP completely inhibited c-EFS-induced contraction whereas neostigmine potentiated c-EFS-induced contraction dose-dependently. P (max) was not increased by neostigmine. P (max) was not increased by 2-Hz c-ES, but was increased by the addition of neostigmine. P (max) was increased by 5-Hz c-ES, and further increased by the addition of neostigmine. CONCLUSION: The contractile response of the tracheal ring to c-EFS is potentiated by neostigmine. P (max) is increased by c-ES of the vagal nerve, and is potentiated by neostigmine. These data suggest that increased activity of the cholinergic nerve could be involved in asthma attack.